Countless things can go wrong, starting with the first step.
The worldwide supply of moly-99 relies on a fleet of government-subsidized nuclear research reactors built mostly during the Khrushchev-Eisenhower era.
Regular maintenance and major repairs can shutter the reactors, sometimes for months, and so-called “scrams” — caused by anything from a hiccup in a reactor’s cooling system to an errant lightning strike — frequently halt production. “It’s a nuclear reactor,” Mr. Charlton said. “The only thing you can do is shut it off.”
Even the Mayo Clinic in Rochester, Minn., a prestigious cancer treatment center, can be left waiting for shipments of the so-called generators that contain the imaging agent. “We’ve had days when no generator comes in at all, or it’s been cut in half,” said Andrew Paulsen, supervisor of the clinic’s radiopharmaceutical laboratory.
And the ephemeral nature of moly-99 always looms. On a recent afternoon, inside a locked laboratory at Stanford University Medical Center’s nuclear medicine department in Palo Alto, Calif., a technician held a lead-lined, plastic cylinder containing a syringe of fragile atoms that had traveled around the globe.
Once the imaging agent is injected into a patient’s body, it emits gamma rays that can be detected by gamma cameras that look like X-ray machines. The radioactive tracer lights up on a computer monitor wherever the heart’s blood vessels are blocked or bones are riddled with potentially cancerous tumors. The imaging agent was first used in medical applications in the 1960s because its short half-life meant that patients were getting less exposure to radioactivity than from other diagnostic tracers.
But at Stanford’s nuclear medicine department that day, a patient had missed his appointment. This meant the dose — which cost the medical center an irretrievable $500 — had decayed and was now useless. The technician threw the syringe in the trash.
The supply chain’s vulnerability, acutely felt during a severe worldwide shortage in 2009 and 2010 when two reactors shut down unexpectedly, has led some doctors to shift to more dependable, but more toxic, imaging agents. “For cardiac imaging, we had to shift to a more expensive agent and expose patients to more radiation,” said Dr. Andrei Iagaru, chief of the division of nuclear medicine at Stanford Health Care.
After the worldwide shortage, the volume of nuclear medicine tests went down, and stayed down. “It definitely had an impact on the way many practices run their cardiac stress tests,” Dr. Iagaru said.
Depending on Other Countries
American patients consume nearly half of the world’s supply of moly-99. And despite plans to ramp up production in Australia, reactor construction is notoriously tricky. In addition, reactors that are converting for security reasons to low-enriched uranium have lower yields and more waste, according to nuclear scientists.
Concerns about moly-99 shortages heightened in October 2016, when the Canadian government mothballed a reactor in Chalk River, Ontario, that supplied about 40 percent of the American market. The government’s decision to shutter the plant was, in part, due to frustration that Canada had had to spend $70 million in 2009 to repair the facility — in effect, subsidizing the American health care industry. That is a complaint of European governments as well.
William Magwood, director of the Nuclear Energy Agency in Paris, said that moly-99 production at Chalk River “went from being incidental to being the only reason to operate the reactor.”
“Canadians didn’t want to continue to operate a high-cost reactor to sell isotopes to the U.S.,” he said.
Some European governments have begun charging moly-99 producers higher rates to rent reactor time, and prices are expected to rise sharply when governments strip for-profit companies of subsidies originally meant to support academic research.
“How much will get passed on to the health care providers?” said Leah Gannon, senior portfolio executive of radiopharmaceutical distribution sourcing for Vizient, a company that negotiates contracts for hospitals. “Probably almost all of it.”
With no source of moly-99 anywhere in North America, American nuclear medicine specialists appointed by the National Academy of Sciences, Engineering and Medicine warned in a 2016 report commissioned by Congress of a more than 50-percent likelihood of another severe shortage in the coming years.
Moly-99 suppliers refute the report’s findings, a position echoed by the Nuclear Energy Agency, which has fostered closer ties between producing nations. Reactor operators, the suppliers say, work closely to stagger maintenance shutdowns to minimize shortages and respond to disruptions in production, and producers have increased the number of uranium targets.
“We’re describing a glass that is half full,” Mr. Charlton said, “whereas the National Academies of Sciences sees the glass looking half empty.”
Still, nuclear medicine physicians and nuclear pharmacists charged with filling patient orders each day say the supply remains fragile, especially for smaller pharmacies where the moly-99 imaging agent can account for 95 percent of their business. “It is inconceivable to believe that an outage will never occur on any of these old reactors in the future,” said Dr. Joseph Hung, director of radiopharmaceutical operations at the Mayo Clinic and a member of the government committee.
Wendy Galbraith, a clinical associate professor at the University of Oklahoma College of Pharmacy in Oklahoma City who runs the university’s pharmacy, said she frequently doesn’t know if moly-99 is going to be available until the wee hours of the morning. Even when there are no major outages, she said, “It’s a scramble.”
That uncertainty means delays and on-the-fly triage for patients. “If we have a patient who can wait two days for their cardiac stress test, we’ll put them off,” Ms. Galbraith said.
Suppliers want to tamp down fears about reliability, physicians and pharmacists say, to dissuade them from seeking alternative imaging methods when possible, like positron emission tomography, a costly and complex type of medical scan.
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